A Helical RGD Motif Promoting Cell Adhesion: Crystal Structures of the Helicobacter pylori Type IV Secretion System Pilus Protein CagL

被引：73

作者：

Barden, Stephan ^{[1
]}

Lange, Stefanie ^{[1
]}

Tegtmeyer, Nicole ^{[2
,3
]}

Conradi, Jens ^{[1
]}

Sewald, Norbert ^{[1
]}

Backert, Steffen ^{[2
,3
]}

Niemann, Hartmut H. ^{[1
]}

机构：

[1] Univ Bielefeld, Dept Chem, D-33501 Bielefeld, Germany

[2] OvG Univ Magdeburg, Inst Med Microbiol, D-39120 Magdeburg, Germany

[3] FAU Univ Erlangen Nuremberg, Dept Biol, D-91058 Erlangen, Germany

来源：

STRUCTURE | 2013年 / 21卷 / 11期

关键词：

PATHOGENICITY ISLAND; LYSINE METHYLATION; INTEGRIN; VIRULENCE; CRYSTALLIZATION; TRANSLOCATION; RECOGNITION; RECEPTORS; INDUCTION; SERVER;

D O I：

10.1016/j.str.2013.08.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

RGD tripeptide motifs frequently mediate ligand binding to integrins. The type IV secretion system (T4SS) protein CagL of the gastric pathogen Helicobacter pylori also contains an RGD motif. CagL decorates the T4SS pilus and may function as an adhesin for host cells. Whether CagL binds integrins via its RGD motif is under debate. Here, we present crystal structures of CagL revealing an elongated four-helix bundle that appears evolutionarily unrelated to the proposed VirB5 orthologs. The RGD motif is surface-exposed but located within a long a helix. This is unprecedented as previously characterized integrin-binding RGD motifs are located within extended or flexible loops. Yet, adhesion of gastric epithelial cells to CagL was strictly RGD-dependent. Comparison of seven crystallographically independent molecules reveals substantial structural flexibility. Intramolecular disulfide bonds engineered to reduce CagL flexibility resulted in more stable protein, but unable to support cell adhesion. CagL may thus partly unfold during receptor binding.

引用

页码：1931 / 1941

页数：11

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